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Jul 10, 2007: National Cancer Institute Bulletin: (back)

This bulletin describes three separate studies that were published in Nature Genetics on June 8, 2007. Markers described herein are the commercial property of ArcticDx Inc. Genetic Markers of Colorectal Cancer Risk Identified. Three separate genome-wide association studies published online July 8 in Nature Genetics have identified a locus on chromosome 8 (8q24) in which several single nucleotide polymorphisms (SNPs) - changes in a single nucleotide of DNA - confer significantly increased risk of colorectal cancer (CRC). This locus has been implicated in previously published research as playing a role in prostate cancer risk.

The first study, led by a Canadian research team, used a four-stage process to identify and validate SNPs associated with CRC risk. The first stage evaluated three different sets of SNPs, containing more than 50,000 single nucleotide changes, in 1,257 people with colorectal cancer and 1,336 controls from Ottawa. The second stage tested 1,143 potential markers of risk identified in stage 1 in two different case-control populations: one from Seattle, Washington, and one from Newfoundland. The third stage tested 76 markers replicated in the previous 3 populations in a case-control population from Scotland with early-onset CRC. The nine markers further validated in this population were then tested in a fourth stage in a second, independent case-control series from Scotland.

Two of the risk associations confirmed in stage 3 were replicated in stage 4, and the investigators compared these loci, 8q24 and 9p24, with results from several European studies, leading to validation of two SNPs in 8q24 that confer significantly increased risk of CRC. This multistep replication process is in keeping with recent guidelines published in Nature by the NCI-NHGRI Working Group on Replication in Association Studies.

DNA Strand